Immunomodulatory effects of non-digestible oligosaccharides in peanut allergy : Treating by eating

Abstract

The prevalence of food allergies is increasing worldwide, particularly but not only in developed countries and has an impact on the quality of life of affected children and adults. Food allergies can develop when immunological tolerance against harmless food allergens is hampered. Currently, no lasting treatment options are available to restore long-lasting tolerance in peanut-allergic patients. Immunotherapeutic approaches aiming to restore tolerance are still under development. Major issues are efficacy and the frequent occurrence of sometimes severe allergic reactions. To further optimize these immunotherapeutic approaches, more interest is gained towards the use of specific adjuvants during immunotherapy, such as anti-IgE antibody omalizumab or even dietary components. The rationale behind the use of dietary adjunct therapy is that these components have immunomodulatory capacities, and may already skew the immune response away from the allergenic phenotype towards a more regulatory or T helper 1 (Th1) phenotype. Hereby they support the immunotherapeutic approaches, rendering them more safe and efficacious. The most important focus of this thesis was the investigation of the immunomodulatory effects of dietary non-digestible oligosaccharide (NDO) mixtures consisting of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS) and short-and long-chain fructo-oligosaccharides (scFOS/lcFOS). Based on previous studies, it was hypothesized that they might be able to contribute to the safety and efficacy of developing approaches for allergen-specific immunotherapy. These immunomodulatory effects were investigated in in vitro models using blood of peanut-allergic patients. The results of this thesis provide valuable insights into the immunomodulatory effects of non-digestible oligosaccharides, as they, for example, can skew the immune function towards a more regulatory and Th1-like phenotype in an in vitro environment. In addition, NDOs were able to reduce basophil degranulation and modify antigen presentation by DCs in the presence of peanut-extract. The development of peanut allergy and food allergy in general is a complex phenomenon, which requires more research to understand, but we hypothesize that adjunct therapy with NDOs in combination with immunotherapy might be the next step in safely inducing long-lasting tolerance in peanut-allergic patients.